There is convincing convergent evidence from family, adoption and twin research for the importance of familial factors in the development of alcohol dependence. Laboratory studies have been conducted with offspring of alcoholics who have not yet themselves developed the disorder in an effort to identify markers associated with the future development of alcoholism. Differences in alcohol sensitivity have been found as a function of familial alcoholism history. More recently, ours and others' research has examined the generalization to other drug classes of this differential sensitivity associated with familial alcoholism. Also, we have previously reported that family history positive youth use marijuana at a greater frequency, report an earlier age of first use of marijuana, and report more problems as a result of drug use than family history negative youth. The proposed research project will examine the role of a family history of alcoholism in modulating responses to marijuana, employing both controlled dosing and self-administration procedures in the laboratory. Subjects will include college-aged males and females with a high density of familial alcoholism and matched comparison groups with no history of familial alcoholism. Experiment 1 will examine the role of familial alcoholism as a determinant of the dose-effects of smoked marijuana (0, 2.5, and 4% THC); ethanol (1 g/kg) also will be administered to allow an explicit comparison of the magnitude of family history group differences in response to these two drugs. Using a self-administration paradigm, Experiment 2 will determine the role of familial alcoholism in modulating the amounts and topography of smoked marijuana across a range of cigarette potencies in the laboratory (0, 1.3, and 2.5% THC). Experiment 3 will examine the interactions between alcohol ingestion and marijuana self-administration in the two family history groups. This study will be important based on earlier demonstrations of differences in alcohol sensitivity as a function of family alcoholism history, and of a priming effect of alcohol on both tobacco and marijuana cigarette smoking behavior. Throughout this project, four broad dimensions of responses will be studied: physiological, psychomotor, subjective, and behavioral. Of particular interest will be smoking topography measures such puff volume, duration and patterning, as well as neuroendocrine measures including ACTH, beta-endorphins, prolactin, and growth hormone. Additional measures that have been shown in our previous research to differentiate the family history groups are self-reports of mood, euphoria and hangover, the autonomic measures of heart rate and skin conductance, as well as psychomotor performance measures such as digit symbol substitution test, and other reaction time and cognitive tasks. Data will be analyzed as a function of both family history and gender factors. If we find differential sensitivity to, and/or differential rates of self-administration of marijuana, this suggests that family-history positive youth may not only be at increased risk for future development of alcoholism, but also at increased risk for the development of other psychoactive substance abuse disorders. These findings will have important implications for targeting limited prevention and treatment resources to these very vulnerable youth.
